Further Studies of Effects of X-Radiation on Partially Shielded Lens of Rabbit

Leinfelder, P.J.; Riley, Edgar F.

doi:10.1001/archopht.1956.00930030086012

Cited by 29 publications

(4 citation statements)

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“…Lens epithelial cells in the germinative zone of the lens epithelium around the equator divide [2] . Rodent cataracts have been reported to occur after the equatorial region was locally irradiated [21] , but not after irradiation when the germinative zone was shielded [22] , [23] , [24] , indicating that cells in the germinative zone are the relevant cells at risk. To our knowledge, only a few papers [25] , [26] , [27] reported the radiation-induced excessive proliferation of lens epithelial cells, ahead of this work Dating back to the 1950s, von Sallman et al observed that excessive proliferation of lens epithelial cells in the germinative zone within 21 days after X-irradiation of the rabbit eye occurred slightly at 125 r, became evident at 250 r and more manifested at higher dose (tested up to 2,000 r) [26] .…”

Section: Discussionmentioning

confidence: 99%

Ionizing Irradiation Not Only Inactivates Clonogenic Potential in Primary Normal Human Diploid Lens Epithelial Cells but Also Stimulates Cell Proliferation in a Subset of This Population

Fujimichi

Hamada

2014

PLoS ONE

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Over the past century, ionizing radiation has been known to induce cataracts in the crystalline lens of the eye, but its mechanistic underpinnings remain incompletely understood. This study is the first to report the clonogenic survival of irradiated primary normal human lens epithelial cells and stimulation of its proliferation. Here we used two primary normal human cell strains: HLEC1 lens epithelial cells and WI-38 lung fibroblasts. Both strains were diploid, and a replicative lifespan was shorter in HLEC1 cells. The colony formation assay demonstrated that the clonogenic survival of both strains decreases similarly with increasing doses of X-rays. A difference in the survival between two strains was actually insignificant, although HLEC1 cells had the lower plating efficiency. This indicates that the same dose inactivates the same fraction of clonogenic cells in both strains. Intriguingly, irradiation enlarged the size of clonogenic colonies arising from HLEC1 cells in marked contrast to those from WI-38 cells. Such enhanced proliferation of clonogenic HLEC1 cells was significant at ≥2 Gy, and manifested as increments of ≤2.6 population doublings besides sham-irradiated controls. These results suggest that irradiation of HLEC1 cells not only inactivates clonogenic potential but also stimulates proliferation of surviving uniactivated clonogenic cells. Given that the lens is a closed system, the stimulated proliferation of lens epithelial cells may not be a homeostatic mechanism to compensate for their cell loss, but rather should be regarded as abnormal. This is because these findings are consistent with the early in vivo evidence documenting that irradiation induces excessive proliferation of rabbit lens epithelial cells and that suppression of lens epithelial cell divisions inhibits radiation cataractogenesis in frogs and rats. Thus, our in vitro model will be useful to evaluate the excessive proliferation of primary normal human lens epithelial cells that may underlie radiation cataractogenesis, warranting further investigations.

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Section: Discussionmentioning

confidence: 99%

Ionizing Irradiation Not Only Inactivates Clonogenic Potential in Primary Normal Human Diploid Lens Epithelial Cells but Also Stimulates Cell Proliferation in a Subset of This Population

Fujimichi

Hamada

2014

PLoS ONE

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“…Support for this hypothesis is provided by animal experiments which demonstrated that radiation cataracts will not form if epithelial cell division is inhibited Rothstein, 1975, 1977;Rothstein et al, 1982; Holsclaw et al, 1989 or if the dividing portion of the lens epithelium is shielded from exposure (Alter and Leinfelder, 1953;Puntenney and Schoch, 1953;Leinfelder and Riley, 1956;Pirie and Flanders, 1957). In this case, radiation cataract development would be stochastic.…”

Section: Dose Response and Cataract Thresholdmentioning

confidence: 99%

“…1982 ;Holsclaw et al, 1989 or if the dividing portion of the lens epithelium is shielded from exposure (Alter and Leinfelder, 1953;Puntenney and Schoch, 1953;Leinfelder and Riley, 1956;Pirie and Flanders, 1957). In this case, radiation cataract development would be stochastic.…”

Section: Dose Response and Cataract Thresholdmentioning

confidence: 99%

ICRP PUBLICATION 118: ICRP Statement on Tissue Reactions and Early and Late Effects of Radiation in Normal Tissues and Organs — Threshold Doses for Tissue Reactions in a Radiation Protection Context

Stewart¹,

Akleyev²,

et al. 2012

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This report provides a review of early and late effects of radiation in normal tissues and organs with respect to radiation protection. It was instigated following a recommendation in Publication 103 (ICRP, 2007), and it provides updated estimates of 'practical' threshold doses for tissue injury defined at the level of 1% incidence. Estimates are given for morbidity and mortality endpoints in all organ systems following acute, fractionated, or chronic exposure. The organ systems comprise the haematopoietic, immune, reproductive, circulatory, respiratory, musculoskeletal, endocrine, and nervous systems; the digestive and urinary tracts; the skin; and the eye. Particular attention is paid to circulatory disease and cataracts because of recent evidence of higher incidences of injury than expected after lower doses; hence, threshold doses appear to be lower than previously considered. This is largely because of the increasing incidences with increasing times after exposure. In the context of protection, it is the threshold doses for very long follow-up times that are the most relevant for workers and the public; for example, the atomic bomb survivors with 40-50years of follow-up. Radiotherapy data generally apply for shorter follow-up times because of competing causes of death in cancer patients, and hence the risks of radiation-induced circulatory disease at those earlier times are lower. A variety of biological response modifiers have been used to help reduce late reactions in many tissues. These include antioxidants, radical scavengers, inhibitors of apoptosis, anti-inflammatory drugs, angiotensin-converting enzyme inhibitors, growth factors, and cytokines. In many cases, these give dose modification factors of 1.1-1.2, and in a few cases 1.5-2, indicating the potential for increasing threshold doses in known exposure cases. In contrast, there are agents that enhance radiation responses, notably other cytotoxic agents such as antimetabolites, alkylating agents, anti-angiogenic drugs, and antibiotics, as well as genetic and comorbidity factors. Most tissues show a sparing effect of dose fractionation, so that total doses for a given endpoint are higher if the dose is fractionated rather than when given as a single dose. However, for reactions manifesting very late after low total doses, particularly for cataracts and circulatory disease, it appears that the rate of dose delivery does not modify the low incidence. This implies that the injury in these cases and at these low dose levels is caused by single-hit irreparable-type events. For these two tissues, a threshold dose of 0.5Gy is proposed herein for practical purposes, irrespective of the rate of dose delivery, and future studies may elucidate this judgement further.

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“…The earliest lenticular changes following irradiation include the formation of ‘vacuoles’ in the equatorial regions, which then appear in the central portion of the posterior cortex and PSC regions [ 100 , 101 ]. These vacuoles appear to be transient in nature [ 102 ] and greatly differ in diameter (e.g.…”

Section: Radiogenic Cataractsmentioning

confidence: 99%

Emerging issues in radiogenic cataracts and cardiovascular disease

Hamada

Fujimichi

Iwasaki

et al. 2014

Journal of Radiation Research

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In 2011, the International Commission on Radiological Protection issued a statement on tissue reactions (formerly termed non-stochastic or deterministic effects) to recommend lowering the threshold for cataracts and the occupational equivalent dose limit for the crystalline lens of the eye. Furthermore, this statement was the first to list circulatory disease (cardiovascular and cerebrovascular disease) as a health hazard of radiation exposure and to assign its threshold for the heart and brain. These changes have stimulated various discussions and may have impacts on some radiation workers, such as those in the medical sector. This paper considers emerging issues associated with cataracts and cardiovascular disease. For cataracts, topics dealt with herein include (i) the progressive nature, stochastic nature, target cells and trigger events of lens opacification, (ii) roles of lens protein denaturation, oxidative stress, calcium ions, tumor suppressors and DNA repair factors in cataractogenesis, (iii) dose rate effect, radiation weighting factor, and classification systems for cataracts, and (iv) estimation of the lens dose in clinical settings. Topics for cardiovascular disease include experimental animal models, relevant surrogate markers, latency period, target tissues, and roles of inflammation and cellular senescence. Future research needs are also discussed.

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Further Studies of Effects of X-Radiation on Partially Shielded Lens of Rabbit

Cited by 29 publications

References 1 publication

Ionizing Irradiation Not Only Inactivates Clonogenic Potential in Primary Normal Human Diploid Lens Epithelial Cells but Also Stimulates Cell Proliferation in a Subset of This Population

Ionizing Irradiation Not Only Inactivates Clonogenic Potential in Primary Normal Human Diploid Lens Epithelial Cells but Also Stimulates Cell Proliferation in a Subset of This Population

ICRP PUBLICATION 118: ICRP Statement on Tissue Reactions and Early and Late Effects of Radiation in Normal Tissues and Organs — Threshold Doses for Tissue Reactions in a Radiation Protection Context

Emerging issues in radiogenic cataracts and cardiovascular disease

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